The objective in a phototherapy procedure is to deliver the light dose to the tissue that accomplishes the desired clinical objective, e.g., in "PUVA" therapy of psoriasis, light therapy of neonatal jaundice, and photodynamic therapy (PDT) of malignant tumors. Tissues are optically turbid media, in which the disposition of radiant energy depends on the light scattering and absorption properties, the dimensions, and interfaces with external media. The utilization of light by chromophores embedded in tissues can be investigated with the experimental and analytical methods of tissue optics. A diffuse optics spectrophotometer utilizing integrating spheres and optical fiber probe methods will be used for the measurements, and the results will be analyzed with the diffusion approximation for radiative transfer. These techniques will be applied to in vitro systems that model the photophysical and photochemical stages of PDT at the molecular level. Tissue phantoms consisting of light scattering liposomes and resealed beef erythrocyte membranes incorporating a hematoporphyrin derivative (HPD) preparation, and selected alternative PDT sensitizers, will be employed to study the effects of wavelengths, sensitizer concentration, and photobleaching on photodynamic efficiency. The HPD preparations to be investigated include the clinical drug Photofrin II, HPD enriched in the active "dihematoporphyrin ether" (DHE) constituent by gel column chromatography, 99% DHE prepared on an a Sephadex LH-20 column (provided by Dr. D. Kessel), and HPD with a high ester content prepared by acetylation with acetic anhydride in pyridine. Lipid peroxidation, cross-linking of ghost proteins, and photoinactivation of exogenous enzyme probes will be employed for damage evaluation. Similar experiments will be done with biological tissues incorporating photosensitizers, including potato slabs and pig skin. The project includes the further development of analytical optical dosimetry models for PDT treatment planning. The models will be tested at the photophysical level with tissue phantoms, and evaluated for applicability be retrospective comparison to on-going PDT trails.